• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Analysis of Surfactant-mediated Dissolution Effects in Biorelevant Media

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    RAMAN_umaryland_0373D_10776.pdf
    Size:
    2.670Mb
    Format:
    PDF
    Download
    Author
    Raman, Siddarth
    Advisor
    Polli, James E.
    Date
    2016
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Food is known to impact drug bioavailability through a variety of mechanisms, including drug solubilization and prolonged gastric residence time. In vitro dissolution media that aim to mimic in vivo gastrointestinal (GI) conditions have been developed to lessen the need for fed human bioequivalence studies. The first aim of this work was to develop an in vitro lipolysis model to predict positive food effect of three BCS Class II drugs (i.e. danazol, amiodarone and ivermectin) in previously developed lipolysis media. The in vitro lipolysis model accurately predicted the in vivo positive food effect for three model BCS class II drugs. The in vitro lipolysis model has potential use as a screening test of drug candidates in early development to assess positive food effect. In vitro lipolysis is an in vitro approach to simulate drug dissolution under fed conditions, in an effort to anticipate when food increases the absorption of poorly water soluble drugs in vivo due to increased drug solubilization. Imaging techniques have promise to aid in understanding such positive food effects. The second aim of this work was to employ cryogenic transmission electron microscopy (cryo-TEM) to characterize the colloidal changes in Fe-Lipolysis during drug dissolution, and correlate food-enhanced dissolution with colloid structures. Danazol was selected as a model BCS Class II drug with a positive food effect. Danazol samples from fed and fasted state dissolution experiments were subjected to cryo-TEM. Compared to the fed state observations, no major changes were observed in the fasted state. These findings concur with in vivo observations and previously developed hypothetical models of lipolysis and drug solubilization. The third aim of the work was to develop a better understanding of surfactant-mediated dissolution effects in biorelevant media. Three poorly soluble drugs, ciprofloxacin HCl, ivermectin and fexofenadine HCl, that differed in their lipophilicity were analyzed using biorelevant dissolution in human as well as canine fasted state intestinal media. The main objective was to compare the rate and extent of dissolution between these drugs and further elucidate the surfactant-mediated enhancements they experienced. Ivermectin displayed significantly slower dissolution than ciprofloxacin HCl and fexofenadine HCl. Using previously derived models of surfactant-mediated dissolution enhancement, it was determined that ivermectin was heavily dependent on the presence of surfactant, while ciprofloxacin and fexofenadine dissolution showed no dependence on the presence of surfactant as a result of being heavily surfactant-independent.
    Description
    University of Maryland, Baltimore. Pharmaceutical Sciences. Ph.D. 2016
    Keyword
    dissolution
    food effect
    surfactant
    Lipolysis
    Surface-Active Agents
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/6277
    Collections
    Theses and Dissertations All Schools
    Theses and Dissertations School of Pharmacy

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.